title: FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis.
abstract: Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue.
authors.affiliation: Genetics of Vertebrate Development Section, National Cancer Institute, Frederick, MD 21701, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Naiche
authors.forename: Nakisha
authors.initials: N
authors.lastname: Holder
authors.forename: Mark
authors.initials: M
authors.lastname: Lewandoski
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D051519:Fibroblast Growth Factor 4 / Q000235:genetics / Q000502:physiology*; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D015398:Signal Transduction; D019170:Somites
chemical_list: C496446:Fgf4 protein, mouse; C496457:Fgf8 protein, mouse; D051519:Fibroblast Growth Factor 4; D051524:Fibroblast Growth Factor 8